Research Topics
Genomes and Genes | Lawrence HaywardSummaryAffiliation: University of Massachusetts Medical School Country: USA Publications
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Publications
Decreased metallation and activity in subsets of mutant superoxide dismutases associated with familial amyotrophic lateral sclerosisLawrence J Hayward
Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
J Biol Chem 277:15923-31. 2002..Further characterization of these as-isolated SOD1 proteins may provide new insights regarding mutant SOD1 enzyme toxicity in ALS...
Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weaknessLawrence J Hayward
Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
J Clin Invest 118:1437-49. 2008....- Familial amyotrophic lateral sclerosis mutants of copper/zinc superoxide dismutase are susceptible to disulfide reductionAshutosh Tiwari
Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
J Biol Chem 278:5984-92. 2003..These results implicate SOD1 destabilization under cellular disulfide-reducing conditions at physiological pH and temperature as a shared property that may be relevant to amyotrophic lateral sclerosis mutant neurotoxicity... - Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granulesDaryl A Bosco
Department of Neurology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
Hum Mol Genet 19:4160-75. 2010..These findings demonstrate a potential link between FUS mutations and cellular pathways involved in stress responses that may be relevant to altered motor neuron homeostasis in ALS... - Inhibition of chaperone activity is a shared property of several Cu,Zn-superoxide dismutase mutants that cause amyotrophic lateral sclerosisHemachand Tummala
Department of Biochemistry and Molecular Pharmacology, Neurology, and Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 280:17725-31. 2005..Thus, mutant SOD1 proteins may impair chaperone function independent of gene expression in vivo, and this inhibition may be a shared property of ALS-linked mutant SOD1 proteins... - Metal deficiency increases aberrant hydrophobicity of mutant superoxide dismutases that cause amyotrophic lateral sclerosisAshutosh Tiwari
Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
J Biol Chem 284:27746-58. 2009..Overall, our findings support the notion that misfolding associated with metal deficiency may facilitate aberrant interactions of SOD1 with itself or with other cellular constituents and may thereby contribute to neuronal toxicity... - Aberrantly increased hydrophobicity shared by mutants of Cu,Zn-superoxide dismutase in familial amyotrophic lateral sclerosisAshutosh Tiwari
Department of Neurology, University of Massachusetts Medical School, Worcester, 01655, USA
J Biol Chem 280:29771-9. 2005..These abnormally hydrophobic SOD1 species may promote aberrant interactions of the enzyme with itself or with other cellular constituents to produce toxicity in familial ALS... - Mutant SOD1 instability: implications for toxicity in amyotrophic lateral sclerosisAshutosh Tiwari
Department of Neurology, University of Massachusetts Medical School, Worcester, 01655, USA
Neurodegener Dis 2:115-27. 2005..The challenge for future investigations is to relate these abnormal properties of partially unfolded SOD1 to specific mechanisms of toxicity in motor neurons, supporting cells, or target tissues... - Familial amyotrophic lateral sclerosis-associated mutations decrease the thermal stability of distinctly metallated species of human copper/zinc superoxide dismutaseJorge A Rodriguez
Department of Chemistry and Biochemistry, UCLA, Los Angeles, California 90095 1569, USA
J Biol Chem 277:15932-7. 2002..We conclude that decreased conformational stability shared by all of these mutant SOD1s may contribute to SOD1 toxicity in FALS... - Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosisXiaohang Cao
Department of Biochemistry and the X ray Crystallography Core Laboratory, The University of Texas Health Ssience Center, San Antonio, Texas 78229, USA
J Biol Chem 283:16169-77. 2008..These findings support the notion that metal-deficient and/or disulfide-reduced mutant SOD1 species contribute to toxicity in SOD1-linked amyotrophic lateral sclerosis... - The structure of holo and metal-deficient wild-type human Cu, Zn superoxide dismutase and its relevance to familial amyotrophic lateral sclerosisRichard W Strange
Molecular Biophysics Group, Department of Synchrotron Radiation, CCLRC Daresbury Laboratory, Warrington, Cheshire, UK
J Mol Biol 328:877-91. 2003.... 
Retrograde axonal transport and motor neuron diseaseAnna Lena Strom
Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
J Neurochem 106:495-505. 2008..We further consider how the interference with axonal transport and protein turnover by mutant SOD1 could influence the function and viability of motor neurons in ALS...- Interaction of amyotrophic lateral sclerosis (ALS)-related mutant copper-zinc superoxide dismutase with the dynein-dynactin complex contributes to inclusion formationAnna Lena Strom
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536, USA
J Biol Chem 283:22795-805. 2008..Whether the misfolded SOD1s directly perturb axonal transport or impair other functional properties of the dynein motor, this interaction could propagate a toxic effect that ultimately causes motor neuron death in ALS... - Detergent-insoluble aggregates associated with amyotrophic lateral sclerosis in transgenic mice contain primarily full-length, unmodified superoxide dismutase-1Bryan F Shaw
Department of Chemistry and Biochemistry, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA
J Biol Chem 283:8340-50. 2008..The results demonstrate that the principal protein in the high molecular mass aggregates whose appearance correlates with symptoms of the disease is the unmodified, full-length SOD1 polypeptide... - Increased affinity for copper mediated by cysteine 111 in forms of mutant superoxide dismutase 1 linked to amyotrophic lateral sclerosisShohei Watanabe
Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka 565 0871, Japan
Free Radic Biol Med 42:1534-42. 2007..Aberrant Cu binding at the Cys111 residue may be a significant factor in altering mutant SOD1 behavior and may explain the benefit of controlling Cu access to mutant SOD1 in models of familial ALS... - Destabilization of apoprotein is insufficient to explain Cu,Zn-superoxide dismutase-linked ALS pathogenesisJorge A Rodriguez
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA
Proc Natl Acad Sci U S A 102:10516-21. 2005..Thus, the ALS mutant Cu,Zn-superoxide dismutase apoproteins do not all share reduced global stability, and additional properties must be identified and understood to explain the toxicity of all of the mutant proteins... - Amyloid-like filaments and water-filled nanotubes formed by SOD1 mutant proteins linked to familial ALSJennifer Stine Elam
Department of Biochemistry and the Center for Biomolecular Structure Analysis, The University of Texas, Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229 3900, USA
Nat Struct Biol 10:461-7. 2003..Loss of this protection through conformational rearrangement in the metal-deficient enzyme could be a toxic property common to mutants of SOD1 linked to FALS... - An alternative mechanism of bicarbonate-mediated peroxidation by copper-zinc superoxide dismutase: rates enhanced via proposed enzyme-associated peroxycarbonate intermediateJennifer Stine Elam
Department of Biochemistry and the X ray Crystallography Core Laboratory, University of Texas Health Science Center, San Antonio, Texas 78229 3900, USA
J Biol Chem 278:21032-9. 2003..The orientation of the enzyme-associated oxyanion suggests that both the self-oxidative and external oxidative pathways can proceed through an enzyme-associated peroxycarbonate intermediate... - Structural consequences of the familial amyotrophic lateral sclerosis SOD1 mutant His46ArgSvetlana Antonyuk
Molecular Biophysics Group, CCLRC Daresbury Laboratory, Warrington, Cheshire, WA4 4AD, UK
Protein Sci 14:1201-13. 2005.... - Dimer destabilization in superoxide dismutase may result in disease-causing properties: structures of motor neuron disease mutantsMichael A Hough
Molecular Biophysics Group, Council for the Central Laboratory of the Research Councils, Daresbury Laboratory, Warrington, Cheshire WA4 4AD, United Kingdom
Proc Natl Acad Sci U S A 101:5976-81. 2004.... - Interaction between familial amyotrophic lateral sclerosis (ALS)-linked SOD1 mutants and the dynein complexFujian Zhang
Graduate Center for Nutritional Sciences, Department of Molecular and Cellular Biochemistry, College of Medicine, Lexington, Kentucky 40536, USA
J Biol Chem 282:16691-9. 2007..The aberrant interaction is potentially critical to the formation of mutant SOD1 aggregates as well as the toxic cascades leading to motor neuron degeneration in ALS...
Research Grants
- Role of SOD Instability in ALS Motor Neuron ToxicityLawrence Hayward; Fiscal Year: 2006..Future results from Aims 1 and 2 may favor alternative hypotheses of mutant SOD1 toxicity to test in these cellular models and may suggest new therapeutic approaches to evaluate in ALS mice. ..